Tivozanib therapy is associated with a reduced risk of disease progression and similar survival compared with sorafenib treatment in patients with highly-relapsed or refractory metastatic renal cell carcinoma (mRCC), according to a final analysis of the TIVO-3 trial presented at the American Society of Clinical Oncology 2020 Virtual Scientific Program.

Tivozanib is a third-generation highly selective vascular endothelial growth factor receptor (VEFGR) tyrosine kinase inhibitor (TKI). Previously reported primary results from TIVO-3, which compared the drugs in patients with mRCC who had received 2 or 3 prior systemic therapies that failed, found that median progression-free survival (PFS) was 5.6 months among the 175 patients who received tivozanib compared with 3.9 months for the 175 patients treated with sorafenib. The median follow-up was 19 months. Results from this primary analysis were published in The Lancet Oncology.

The final analysis, with a median follow-up of 38 months for tivozanib and 40 months for sorafenib, revealed no significant difference in median overall survival (OS) survival in the tivozanib and sorafenib groups (16.4 vs 19.2 months, respectively), Sumanta K. Pal, MD, of the City of Hope National Medical Center in Duarte, California, and colleagues reported.

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Of the 350 patients in the study, 60% had received 2 prior lines of therapy and 40% had received 3 prior lines. With regard to prior treatments, 45% and 46% of the tivozanib and sorafenib arms received 2 VEGFR TKIs, respectively, 27% and 25% received a checkpoint inhibitor (CPI) plus a VEFGR TKI, and 28% and 29% received a VEGFR TKI plus another drug.

According to the researchers, the greatest benefit was observed among patients who had received prior CPI and a VEGFR TKI or 2 VEGFR TKIs. These patients experienced a significant 45% and 43% decreased risk of progression, respectively.

For the checkpoint inhibitor plus VEGFR TKI recipients, the objective response rate was significantly higher for the tivozanib than sorafenib recipients (24% vs 6.8%).

“In summary, tivozanib significantly improved progression-free survival and response rates with similar overall survival and improved tolerability to sorafenib in patients with highly treatment-refractory advanced renal cell carcinoma across several patient subgroups,” Dr Pal said in a video presentation about the poster. “Tivozanib was well tolerated with fewer dose interruptions, reductions, and discontinuations compared to the active comparator sorafenib. The benefit was most notable in patients previously treated with a checkpoint inhibitor or 2 prior TKIs.”

He added that while emerging data continue to provide guidance on the best first- and second-line treatment, “there continues to be an urgent need in this case to provide robust clinical studies that inform effective and tolerable treatments in the highly refractory setting. The TIVO-3 results represent the first phase 3 prospective data to inform treatment decisions for patients with advanced renal cell carcinoma in later lines of therapy, especially in patients previously treated with VEGF TKIs and checkpoint inhibitors.”


Pal SK, Escudier B, Atkins MB, et al. TIVO-3: final OS analysis of a randomized, controlled, multi-center, open-label, phase 3 study to compare tivozanib to sorafenib in subjects with metastatic renal cell carcinoma (RCC). Presented at the American Society of Clinical Oncology 2020 Virtual Scientific Program held May 29-31. Abstract 5062.


Rini BI, Pal SK, Escudier BJ, et al. Tivozanib versus sorafenib in patients with advanced renal cell carcinoma (TIVO-3) A phase 3, multicentre, randomised, controlled, open-label study. Lancet Oncol. 2020;21:95-104. doi: 10.1016/S1470-2045(19)30735-1